From heroes to vulnerable victims: labelling Christian Turks as genuine refugees in the 1970s

Abstract

In 1975, the first Christian Turks applied for asylum in the Netherlands. They were at first denied, and only in the early 1980s did they finally begin to win refugee status from the Dutch government. In the meantime, they faced years of uncertainty. Campaigns of lobbyists in the years between 1977 and 1983 contributed to end their waiting. Their campaigns caused a drastic change of the image of the ‘deserving refugee’ in the Netherlands. This article explores the arguments that lobbyists used to influence decision-makers. It shows how and why the public and political image of the ‘deserving refugee’ had to change in order to successfully claim refugee status.     

Widespread state-dependent shifts in cerebellar activity in locomoting mice

Excitatory drive enters the cerebellum via mossy fibers, which activate granule cells, and climbing fibers, which activate Purkinje cell dendrites. Until now, the coordinated regulation of these pathways has gone unmonitored in spatially resolved neuronal ensembles, especially in awake animals. We imaged cerebellar activity using functional two-photon microscopy and extracellular recording in awake mice locomoting on an air-cushioned spherical treadmill. We recorded from putative granule cells, molecular layer interneurons, and Purkinje cell dendrites in zone A of lobule IV/V, representing sensation and movement from trunk and limbs. Locomotion was associated with widespread increased activity in granule cells and interneurons, consistent with an increase in mossy fiber drive. At the same time, dendrites of different Purkinje cells showed increased co-activation, reflecting increased synchrony of climbing fiber activity. In resting animals, aversive stimuli triggered increased activity in granule cells and interneurons, as well as increased Purkinje cell co-activation that was strongest for neighboring dendrites and decreased smoothly as a function of mediolateral distance. In contrast with anesthetized recordings, no 1-10 Hz oscillations in climbing fiber activity were evident. Once locomotion began, responses to external stimuli in all three cell types were strongly suppressed. Thus climbing and mossy fiber representations can shift together within a fraction of a second, reflecting in turn either movement-associated activity or external stimuli.     

Sympatric population divergence within a highly pelagic seabird species complex (Hydrobates spp.)

Both physical and non‐physical barriers can restrict gene flow among seabird populations. Understanding the relative importance of non‐physical barriers, such as breeding phenology, is key to understanding seabird biodiversity. We investigated drivers of diversification in the Leach's storm‐petrel species complex (Hydrobates spp.) by examining population genetic structure across its range. Variation in the mitochondrial control region and six microsatellite loci was assayed in birds sampled from breeding colonies throughout the North Atlantic and North Pacific (H. leucorhoa leucorhoa), as well as from San Benito Islands (H. l. chapmani), and two seasonal populations in Guadalupe (summer breeding H. socorroensis and winter breeding H. cheimomnestes), Mexico. Weak but significant differentiation was found between populations of H. l. leucorhoa breeding in the Atlantic versus North Pacific, as well as between H. l. chapmani and H. l. leucorhoa, and between H. socorroensis and H. cheimomnestes within Guadalupe. In contrast, strong differentiation in both mitochondrial DNA and microsatellites was found between H. leucorhoa and both H. socorroensis and H. cheimomnestes. Phylogenetic reconstruction suggested the Guadalupe seasonal breeding populations are sister taxa, at least in their mitochondrial DNA. Non‐physical barriers to gene flow appear to be more important than physical barriers in driving divergence within the Leach's storm‐petrel species complex. In particular, allochronic speciation may have occurred between the seasonal populations within Guadalupe. Further work should include higher resolution sequencing to confirm results, and an increased sampling effort, particularly within the California area, to fully resolve the relationship between H. l. leucorhoa and H. l. chapmani.     

Application of Physiologically Based Absorption Modeling to Formulation Development of a Low Solubility,Low Permeability Weak Base: Mechanistic Investigation of Food Effect

Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the underlying mechanisms of the observed positive food effect of compound X (cpd X) and to strategically explore the feasible approaches to mitigate the food effect. Cpd X is a weak base with pH-dependent solubility; the compound displays significant and dose-dependent food effect in humans, leading to a nonadherence of drug administration. A GastroPlus Opt logD Model was selected for pharmacokinetic simulation under both fasted and fed conditions, where the biopharmaceutic parameters (e.g., solubility and permeability) for cpd X were determined in vitro, and human pharmacokinetic disposition properties were predicted from preclinical data and then optimized with clinical pharmacokinetic data. A parameter sensitivity analysis was performed to evaluate the effect of particle size on the cpd X absorption. A PBPK model was successfully developed for cpd X; its pharmacokinetic parameters (e.g., C _max, AUC_inf, and t _max) predicted at different oral doses were within ±25% of the observed mean values. The in vivo solubility (in duodenum) and mean precipitation time under fed conditions were estimated to be 7.4- and 3.4-fold higher than those under fasted conditions, respectively. The PBPK modeling analysis provided a reasonable explanation for the underlying mechanism for the observed positive food effect of the cpd X in humans. Oral absorption of the cpd X can be increased by reducing the particle size (<100 nm) of an active pharmaceutical ingredient under fasted conditions and therefore, reduce the cpd X food effect correspondingly.     

Timing and abundance as key mechanisms affecting trophic interactions in variable environments

Climatic changes are disrupting otherwise tight trophic interactions between predator and prey. Most of the earlier studies have primarily focused on the temporal dimension of the relationship in the framework of the match–mismatch hypothesis. This hypothesis predicts that predator's recruitment will be high if the peak of the prey availability temporally matches the most energy‐demanding period of the predators breeding phenology. However, the match–mismatch hypothesis ignores the level of food abundance while this can compensate small mismatches. Using a novel time‐series model explicitly quantifying both the timing and the abundance component for trophic relationships, we here show that timing and abundance of food affect recruitment differently in a marine (cod/zooplankton), a marine–terrestrial (puffin/herring) and a terrestrial (sheep/vegetation) ecosystem. The quantification of the combined effect of abundance and timing of prey on predator dynamics enables us to come closer to the mechanisms by which environment variability may affect ecological systems.     

Climate,copepods and seabirds in the boreal Northeast Atlantic – current state and future outlook

The boreal Northeast Atlantic is strongly affected by current climate change, and large shifts in abundance and distribution of many organisms have been observed, including the dominant copepod Calanus finmarchicus, which supports the grazing food web and thus many fish populations. At the same time, large‐scale declines have been observed in many piscivorous seabirds, which depend on abundant small pelagic fish. Here, we combine predictions from a niche model of C. finmarchicus with long‐term data on seabird breeding success to link trophic levels. The niche model shows that environmental suitability for C. finmarchicus has declined in southern areas with large breeding seabird populations (e.g. the North Sea), and predicts that this decline is likely to spread northwards during the 21st century to affect populations in Iceland and the Faroes. In a North Sea colony, breeding success of three common piscivorous seabird species [black‐legged kittiwake (Rissa tridactyla), common guillemot (Uria aalge) and Atlantic puffin (Fratercula arctica)] was strongly positively correlated with local environmental suitability for C. finmarchicus, whereas this was not the case at a more northerly colony in west Norway. Large seabird populations seem only to occur where C. finmarchicus is abundant, and northward distributional shifts of common boreal seabirds are therefore expected over the coming decades. Whether or not population size can be maintained depends on the dispersal ability and inclination of these colonial breeders, and on the carrying capacity of more northerly areas in a warmer climate.     

Efficient APC/C substrate degradation in cells undergoing mitotic exit depends on K11 ubiquitin linkages

The ubiquitin proteasome system (UPS) directs programmed destruction of key cellular regulators via posttranslational modification of its targets with polyubiquitin chains. These commonly contain Lys-48 (K48)–directed ubiquitin linkages, but chains containing atypical Lys-11 (K11) linkages also target substrates to the proteasome—for example, to regulate cell cycle progression. The ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C) controls mitotic exit. In higher eukaryotes, the APC/C works with the E2 enzyme UBE2S to assemble K11 linkages in cells released from mitotic arrest, and these are proposed to constitute an improved proteolytic signal during exit from mitosis. We tested this idea by correlating quantitative measures of in vivo K11-specific ubiquitination of individual substrates, including Aurora kinases, with their degradation kinetics tracked at the single-cell level. All anaphase substrates tested by this methodology are stabilized by depletion of K11 linkages via UBE2S knockdown, even if the same substrates are significantly modified with K48-linked polyubiquitin. Specific examination of substrates depending on the APC/C coactivator Cdh1 for their degradation revealed Cdh1-dependent enrichment of K11 chains on these substrates, whereas other ubiquitin linkages on the same substrates added during mitotic exit were Cdh1-independent. Therefore we show that K11 linkages provide the APC/C with a means to regulate the rate of substrate degradation in a coactivator-specified manner.     

Satellite telemetry reveals post-breeding movements of Atlantic puffins <Emphasis Type="Italic">Fratercula arctica</Emphasis> from Røst,North Norway

In 3 different years we glued 29-g satellite transmitters to the back feathers of five Atlantic puffins Fratercula arctica breeding in Røst, southwest of the Lofoten Islands. The birds were tracked for a mean of 26 (range 7–46) days, and four were re-sighted (without transmitters) at their nest sites in the following year. The trajectories documented a unidirectional post-breeding migration towards the Barents Sea, completely opposite of that indicated by all but 1 of the 27 existing ring recoveries of adult puffins from colonies in North Norway outside the breeding season. We discuss the importance of what seems to be a regular visit to the Barents Sea in early autumn for puffins from Røst, which is still one of the largest puffin colonies in the world.     

Ocean climate prior to breeding affects the duration of the nestling period in the Atlantic puffin

Time-series covering 23 years for a long-lived seabird, the Atlantic puffin (Fratercula arctica L.) at R?st, northern Norway, was used to explore any indirect effects of climatic variations on chick production. By fitting statistical models on the duration of the nestling period, we found that it may be estimated using the average sea temperature and salinity at 0-20 m depth in March (having a positive and a negative effect, respectively). We propose that when the phytoplankton bloom occurs in early spring, adverse oceanographic conditions, i.e. low temperature and high salinity in March, have a negative effect on puffin reproduction by degradation of the prey availability (mainly Clupea harengus) for chick-feeding adults three months later.     

Transendocardial cell injection is not superior to intracoronary infusion in a porcine model of ischaemic cardiomyopathy: a study on delivery efficiency

Stem cell therapy is a new strategy for chronic ischaemic heart disease in patients. However, no consensus exists on the most optimal delivery strategy. This randomized study was designed to assess cell delivery efficiency of three clinically relevant strategies: intracoronary (IC) and transendocardial (TE) using electromechanical mapping guidance (NOGA) compared to surgical delivery in a chronic pig model of ischaemic cardiomyopathy. Twenty‐four animals underwent delivery of 10⁷ autologous Indium‐oxine‐labelled bone marrow‐derived mesenchymal stem cells (MSC) 4 weeks after infarction and were randomized to one of three groups (n = 8 each group): IC, TE or surgical delivery (reference group). Primary endpoint was defined as percentage (%) of injected dose per organ and assessed by in vivo gamma‐emission counting. In addition, troponin and coronary flow were assessed before and after MSC injection. Blinded endpoint analysis showed no significant difference in efficiency after surgical (16 ± 4%), IC (11 ± 1%) and TE (11 ± 3%) (P = 0.52) injections. IC showed less variability in efficiency compared with TE and surgical injection. Overall, TE injection showed less distribution of MSC to visceral organs compared with other modalities. Troponin rise and IC flow did not differ between the percutaneous groups. This randomized study showed no significant difference in cell delivery efficiency to the myocardium in a clinically relevant ischaemic large animal model between IC and TE delivery. In addition, no differences in safety profile were observed. These results are important in view of the choice of percutaneous cell delivery modality in future clinical stem cell trials.